| First Author | Sharma D | Year | 2021 |
| Journal | PLoS Genet | Volume | 17 |
| Issue | 12 | Pages | e1009982 |
| PubMed ID | 34928956 | Mgi Jnum | J:317430 |
| Mgi Id | MGI:6853930 | Doi | 10.1371/journal.pgen.1009982 |
| Citation | Sharma D, et al. (2021) HES1 is a novel downstream modifier of the SHH-GLI3 Axis in the development of preaxial polydactyly. PLoS Genet 17(12):e1009982 |
| abstractText | Sonic Hedgehog/GLI3 signaling is critical in regulating digit number, such that Gli3-deficiency results in polydactyly and Shh-deficiency leads to digit number reductions. SHH/GLI3 signaling regulates cell cycle factors controlling mesenchymal cell proliferation, while simultaneously regulating Grem1 to coordinate BMP-induced chondrogenesis. SHH/GLI3 signaling also coordinates the expression of additional genes, however their importance in digit formation remain unknown. Utilizing genetic and molecular approaches, we identified HES1 as a downstream modifier of the SHH/GLI signaling axis capable of inducing preaxial polydactyly (PPD), required for Gli3-deficient PPD, and capable of overcoming digit number constraints of Shh-deficiency. Our data indicate that HES1, a direct SHH/GLI signaling target, induces mesenchymal cell proliferation via suppression of Cdkn1b, while inhibiting chondrogenic genes and the anterior autopod boundary regulator, Pax9. These findings establish HES1 as a critical downstream effector of SHH/GLI3 signaling in the development of PPD. |
